Microfluidic Manufacturing of SN-38-Loaded Polymer Nanoparticles with Shear Processing Control of Drug Delivery Properties
| dc.contributor.author | Cao, Yimeng | |
| dc.contributor.author | Silverman, Lisa | |
| dc.contributor.author | Lu, Changhai | |
| dc.contributor.author | Hof, Rebecca | |
| dc.contributor.author | Wulff, Jeremy E. | |
| dc.contributor.author | Moffitt, Matthew G. | |
| dc.date.accessioned | 2021-06-27T14:45:21Z | |
| dc.date.available | 2021-06-27T14:45:21Z | |
| dc.date.copyright | 2019 | en_US |
| dc.date.issued | 2019 | |
| dc.description.abstract | Two-phase gas–liquid microfluidic reactors provide shear processing control of SN-38-loaded polymer nanoparticles (SN-38-PNPs). We prepare SN-38-PNPs from the block copolymer poly(methyl caprolactone-co-caprolactone)-block-poly(ethylene oxides) (P(MCL-co-CL)-b-PEO) using bulk and microfluidic methods and at different drug-to-polymer loading ratios and on-chip flow rates. We show that, as the microfluidic flow rate (Q) increases, encapsulation efficiency and drug loading increase and release half times increase. Slower SN-38 release is obtained at the highest Q value (Q = 400 μL/min) than is achieved using a conventional bulk preparation method. For all SN-38-PNP formulations, we find a dominant population (by number) of nanosized particles (<50 nm) along with a small number of larger aggregates (>100 nm). As Q increases, the size of aggregates decreases through a minimum and then increases, attributed to a flow-variable competition of shear-induced particle breakup and shear-induced particle coalescence. IC25 and IC50 values of the various SN-38-PNPs against MCF-7 cells show strong flow rate dependencies that mirror trends in particle size. SN-38-PNPs manufactured on-chip at intermediate flow rates show both minimum particle sizes and maximum potencies with a significantly lower IC25 value than the bulk-prepared sample. Compared to conventional bulk methods, microfluidic shear processing in two-phase reactors provides controlled manufacturing routes for optimizing and improving the properties of SN-38 nanomedicines. | en_US |
| dc.description.reviewstatus | Reviewed | en_US |
| dc.description.scholarlevel | Faculty | en_US |
| dc.description.sponsorship | We are grateful to the Natural Sciences and Engineering Research Council of Canada, NSERC, for financial support | en_US |
| dc.identifier.citation | Cao, Y., Silverman, L., Lu, C., Hof, R., Wulff, J. E., & Moffitt, M. G. (2019). Microfluidic Manufacturing of SN-38-Loaded Polymer Nanoparticles with Shear Processing Control of Drug Delivery Properties. Molecular Pharmaceutics, 16(1), 96-107. https://doi.org/10.1021/acs.molpharmaceut.8b00874. | en_US |
| dc.identifier.uri | https://doi.org/10.1021/acs.molpharmaceut.8b00874 | |
| dc.identifier.uri | http://hdl.handle.net/1828/13072 | |
| dc.language.iso | en | en_US |
| dc.publisher | Molecular Pharmaceutics | en_US |
| dc.subject | drug delivery | |
| dc.subject | microfluidics | |
| dc.subject | polymer nanoparticles | |
| dc.subject | SN-38 | |
| dc.subject.department | Department of Chemistry | |
| dc.title | Microfluidic Manufacturing of SN-38-Loaded Polymer Nanoparticles with Shear Processing Control of Drug Delivery Properties | en_US |
| dc.type | Postprint | en_US |